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Cheng-Hao Huang,1,2 Mei-Chen Lin,3,4 I-Ching Chou,5,6 Ching-Liang Hsieh2,7,8 1Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung City, 40402, Taiwan; 2Department of Chinese Medicine, China Medical University Hospital, Taichung City, 40447, Taiwan; 3Management Office for Health Data, China Medical University Hospital, Taichung, 40447, Taiwan; 4College of Medicine, China Medical University, Taichung, 40402, Taiwan; 5School of Chinese Medicine, China Medical University, Taichung City, 40402, Taiwan; 6Division of Pediatric Neurology, China Medical University Children’s Hospital, Taichung City, 40447, Taiwan; 7Chinese Medicine Research Center, China Medical University, Taichung City, 40402, Taiwan; 8Graduate Institute of Acupuncture Science, China Medical University, Taichung City, 40402, TaiwanCorrespondence: Ching-Liang Hsieh, Graduate Institute of Acupuncture Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan, Tel +886-4-22053366 ext. 3128, Fax +886-4-22037690, Email clhsieh@mail.cmuh.org.twBackground: Migraine is a recurrent headache disease that has been identified as a risk factor for subsequent dementia. The present study collected data from Taiwan’s National Health Insurance Research Database (NHIRD) to investigate the incidence of dementia in patients with migraine who did or did not concurrently receive acupuncture treatment.Methods: A 1:1 propensity score method was used to match an equal number of patients (N = 4813) in the acupuncture and nonacupuncture cohorts based on sex, age, migraine diagnosis year, index year, insurance amount, urbanization level, baseline comorbidities, and medication usage. We employed Cox proportional hazards models to evaluate the risk of dementia.Results: Patients with migraine who received acupuncture treatment were found to have a lower risk of dementia (adjusted hazard ratio [aHR] = 0.51, 95% CI = 0.40– 0.65) than those who did not undergo acupuncture treatment. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the nonacupuncture cohort (Log rank test, p < 0.001). This propensity score–matched cohort study demonstrated an association between acupuncture treatment and dementia development in patients with migraine in Taiwan.Conclusion: The results suggest that acupuncture treatment significantly reduced the development of dementia in patients with migraine.Keywords: acupuncture, migraine, dementia, National Health Insurance Research Database, NHIRD, propensity score, cohort

James Cheng-Chung Wei,1– 3 Yi-Jung Chang,4 Yu-Hsun Wang,5 Chih-Jung Yeh6 1Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; 2Institute of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan; 3Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; 4Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; 5Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan; 6Department of Public Health, Chung Shan Medical University, Taichung, TaiwanCorrespondence: Chih-Jung Yeh, Department of Public Health, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, South District, Taichung, 40201, Taiwan, Tel +886 4 24739595 #11794, Fax +886 4 24637389, Email alexyeh@csmu.edu.twBackground: Previous research has pointed to the relationship between psoriasis and the development of gout. However, most previous studies had either small sample sizes or short study durations. Therefore, in this nationwide cohort study, we investigated the effect of psoriasis on the risk of gout development.Methods: The study group included one million patients from Taiwan, whom we followed for 14 years. The participants were divided into two cohorts designated as psoriasis and non-psoriasis. A 1:4 propensity score matching test was used to compare age, sex, and index year between the two cohorts. Cox proportional hazard regression was used to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of gout. Sensitivity analyses were conducted to evaluate the HR for gout after the occurrence of psoriasis.Results: The incidence densities of gout in the psoriasis and non-psoriasis cohorts were 6.96 and 5.09 per 1000 person-years, respectively. After adjusting for age, sex, urbanization, comorbidities, and nonsteroidal anti-inflammatory drug (NSAID) use, the adjusted hazard ratio (aHR) with 95% CI for incidental gout in the psoriasis group was 1.38 (1.2– 1.6). Moreover, the aHR (95% CI) values for gout risk in patients with psoriasis using NSAIDs and those who did not were 1.21 (1.0– 1.47) and 1.65 (1.33– 2.05), respectively.Conclusion: This study demonstrated an association between psoriasis and risk of developing gout. Clinically, patients with psoriasis should be evaluated for incidental gout.Keywords: psoriasis, gout, epidemiology, corticosteroids, NHIRD, cohort

Kuan-Yu Chen,1 Ming-Cheng Huang,2,3 Cheng-Li Lin,4 Yu-Chen Lee,2,3,5 Mei-Yao Wu,2,6,&ast; Hung-Rong Yen2,3,7– 9,&ast; 1Department of Chinese Medicine, Taipei City Hospital, Yangming Branch, Taipei, Taiwan; 2Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan; 3Graduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 4Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; 5Graduate Institute of Acupuncture Science, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 6School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 7Research Center for Traditional Chinese Medicine, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; 8Chinese Medicine Research Center, China Medical University, Taichung, Taiwan; 9Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Hung-Rong YenGraduate Institute of Chinese Medicine, School of Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung, 404328, TaiwanTel +886-4-22053366 ext. 3001Fax +886-4-22365141Email hungrongyen@mail.cmu.edu.twMei-Yao WuSchool of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, 91 Hsueh-Shih Road, North District, Taichung, 404328, TaiwanTel +886-4-22052121 ext. 4561Fax +886-4-22037690Email meiyaowu0919@gmail.comBackground: Depression is one of the most disabling disorders, which causes long-term complications such as neurodegenerative disorder and cerebrovascular disease. Some patients with depression seek acupuncture treatment. We aimed to investigate the association between acupuncture treatment and the risk of dementia in patients with depression from the perspective of real-world evidence.Methods: Patients over 18 years old and newly diagnosed with depression between 1997 and 2010 were selected from the Taiwanese National Health Insurance Research Database and followed up until the end of 2013. Propensity score was used to match equal numbers of patients 1:1 (N = 16,609 per group) into acupuncture and non-acupuncture cohorts based on characteristics including sex, age, baseline comorbidity and drug use. The outcome measurement was the comparison of dementia incidence in the two cohorts.Results: Compared with the non-acupuncture cohort, patients who received acupuncture treatment had a decreased risk of dementia (adjusted hazard ratio (aHR) = 0.54; 95% confidence interval (CI) = 0.50– 0.58, P < 0.001) after adjustment for age, sex, comorbidities and drug use. Compared with depression patients who did not receive acupuncture, the aHR of vascular dementia and Alzheimer’s disease incidences for patients who had acupuncture therapy was 0.59 (95% CI 0.48– 0.71) and 0.51 (95% CI 0.39– 0.67), respectively. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the non-acupuncture cohort (Log rank test, p < 0.001).Conclusion: The present study from real-world data revealed that acupuncture reduced the risk of dementia in depression patients, which supports healthcare decisions in clinical practice.Keywords: acupuncture, Alzheimer’s disease, depression, dementia, National Health Insurance Research Database, NHIRD, traditional Chinese medicine

Ing-Luen Shyu,1,2 Li-Yu Hu,3 Yi-Jen Chen,1,4,5 Peng-Hui Wang,1,4,5 Ben-Shian Huang1,4,5 1Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan; 2Department of Obstetrics and Gynecology, Chi-Mei Hospital, Tainan City, Taiwan; 3Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; 4Department of Obstetrics and Gynecology, School of Medicine, Taipei, Taiwan; 5Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan Introduction: Depression might affect women with cervical cancer and can deteriorate their quality of life or even their compliance with cancer treatments. The aim of this study was to investigate the incidence of depression and risk factors for developing depression among women with cervical cancer in Taiwan. Patients and methods: This study enrolled patients with newly diagnosed cervical cancer from the National Health Insurance Research Database in Taiwan. From a population of 21,400,826 residents, each cervical cancer patient was matched with one subject without cervical cancer according to sex, age, and comorbidities with the same diagnostic index. The International Classification of Diseases, Ninth Revision, code 180.9 was used to identify patients with cervical cancer, and 296.0X–296.1X, 296.4X–296.8X, 296.2X–296.3X, 300.4, and 311.X codes were used to identify those with depressive disorders.Results: In total, 19,316 newly diagnosed cervical cancer patients were enrolled from January 2000 to December 2005, and the median follow-up period was 5.23 years (1.75–8.48 years). The prevalence of depressive disorder was 4.21% (813 of 19,316) in the cervical cancer cohort, and it was 3.85% (744 of 19,316) in the control cohort. The incidence risk ratio of depressive disorders was 1.35 (95% CI =1.22–1.49, P

Ying-Hsu Chang,1,2,* Su-Wei Chang,3,4,* Chung-Yi Liu,1,2 Po-Hung Lin,1,2 Kai-Jie Yu,1,2 See-Tong Pang,1,2 Cheng-Keng Chuang,1,2 Hung-Cheng Kan,1,2 I-Hung Shao1,2 1Division of Urology, Department of Surgery, LinKou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 2Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan; 4Division of Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan *These authors contributed equally to this work Introduction: Renal cell carcinoma (RCC) is one of the most lethal urological malignancies, and surgeries remain the mainstay for localized RCC. This study aimed to compare the selection of open surgery and minimally invasive kidney surgery for RCCs for the aspects of complication, medical costs, and patient preference. Materials and methods: We conducted a population-based case–control study by using the National Health Insurance Research Database of Taiwan, which included data from 23 million Taiwanese residents. Patients newly diagnosed with RCC during 2006–2012 were included. We compared the general characteristics, underlying disease, complications, hospital stay, postoperative analgesic dosage, and medical costs between open group and minimally invasive group. Results: A total of 3,172 patients who received radical nephrectomy (RN) or partial nephrectomy (PN) for RCC were included. The mean age was 61.1 years, with a male to female ratio of 1.88. In the minimally invasive groups, the mean hospital stay was significantly shorter than in open groups (12.4 days in open RN versus 10.3 days in minimally invasive RN, and 9.7 days in open PN versus 8.2 days in minimally invasive PN). There was no significant difference between the medical costs and the incidence of major bleeding complication between the open group and the minimally invasive group. Female patients and patients with higher monthly income were more likely to receive minimally invasive surgery. Conclusion: During past decades, open RN has gradually been replaced by minimally invasive surgeries and PN. Compared to open surgeries, minimally invasive surgeries could lead to less postoperative pain and faster recovery. Economic status of the patients potentially hinders them from receiving minimally invasive surgeries, which may cost more. Keywords: renal cell carcinoma, minimally invasive, open surgery, complication, NHIRD

Introduction: Accumulating evidence suggests that metformin reduces incident cancer development. Few cohort studies have evaluated the risk of subsequent cancer development in diabetic cohorts receiving antidiabetic monotherapy. We conducted a population-based study in patients with new-onset type 2 diabetes treated with antidiabetic monotherapy., Methods: We identified a cohort of patients with type 2 diabetics aged ≥30 years receiving hypoglycemic monotherapy (n=7,325) from the 1998-2007 Longitudinal Health Insurance Dataset. Patients were grouped according to the antidiabetic therapy they received into metformin (n=2,223), sulfonylurea (n=3,965), glitazone (n=53), meglitinide (n=128), acarbose (n=150), and insulin (n=806) groups. Patients with preexisting cancer were excluded. All patients were followed up until cancer development, dropout, death, or until December 31, 2008. Cox's model was used to estimate multivariable hazard ratios (HRs) adjusted for age, sex, Charlson comorbidity index, smoking-related comorbidities, alcohol use disorders, morbid obesity, pancreatitis, hypertension, monthly income, and urbanization level. The log-rank test was used to compare cumulative cancer incidence. Two-sided P-values <0.05 were required to reject the null hypothesis., Results: The overall median follow-up duration was 2.5 years (interquartile range, 3.6 years). Totally, 367 and 124 cancers developed in the sulfonylurea and metformin groups, respectively, representing an adjusted HR of 1.36 (95% confidence interval [CI], 1.11-1.67; P<0.005). No significant differences were observed between other groups. Increased adjusted HRs were observed for colorectal cancer (adjusted HR, 1.94; 95% CI, 1.15-3.27; P<0.05) and lung cancer (adjusted HR, 1.76; 95% CI, 1.00-3.07; P<0.05)., Conclusion: Metformin monotherapy may be associated with a reduction in the risk for cancer development compared with sulfonylurea monotherapy. Moreover, the use of an average defined daily dose of >0.25 of metformin when compared to lower dose will contribute to a reduction of 80% risk.

Background: Recent studies have shown that inhaled corticosteroids (ICS) can exert anti-inflammatory effects for chronic airway diseases, and several observational studies suggest that they play a role as cancer chemopreventive agents, particularly against lung cancer. We aimed to examine whether regular ICS use was associated with a reduced risk for future malignancy in patients with newly diagnosed adult-onset asthma., Methods: We used a population-based cohort study between 2001 and 2008 with appropriate person-time analysis. Participants were followed up until the first incident of cancer, death, or to the end of 2008. The Cox model was used to derive an adjusted hazard ratio (aHR) for cancer development. Kaplan-Meier cancer-free survival curves of two groups were compared., Results: The exposed group of 2,117 regular ICS users and the nonexposed group of 17,732 non-ICS users were assembled. After 7,365 (mean, 3.5 years; standard deviation 2.1) and 73,789 (mean, 4.1 years; standard deviation 2.4) person-years of follow-up for the ICS users and the comparator group of non-ICS users, respectively, the aHR for overall cancer was nonsignificantly elevated at 1.33 with 95% confidence interval (CI), 1.00-1.76, P=0.0501. The Kaplan-Meier curves for overall cancer-free proportions of both groups were not significant (log-rank, P=0.065). Synergistic interaction of concurrent presence of regular ICS use was conducted using "ICS-negative and chronic obstructive pulmonary disease (COPD)-negative" as the reference. The aHR for the group of "ICS-positive, COPD-negative" did not reach statistically significant levels with aHR at 1.38 (95% CI, 0.53-3.56). There was a statistically significant synergistic interaction of concurrent presence of regular ICS use and COPD with aHR at 3.78 (95% CI, 2.10-6.81)., Conclusion: The protective effect of regular ICS use in the studied East Asian patients with adult-onset asthma was not detectable, contrary to reports of previous studies that ICS might prevent the occurrence of future cancer.